[unreadable] [unreadable] The proposed investigation will apply a classical conditioning paradigm using galvanic skin response and fMRI to explore the neural correlates of pain perception and its anticipation in chronic cannabis users experiencing peak withdrawal. The scientific aim is to understand the neurophysiologic correlates of psychological dependence on cannabis. Since processing pain is an integral function of the reward pathways implicated in drug dependence, understanding how chronic cannabis smokers in peak withdrawal differ in pain sensitivity and anticipation compared to non-cannabis smokers is an important step toward understanding how and why the brains of chronic cannabis smokers differ from non-smokers. It is proposed that cannabis use masks pain perception, therefore evaluation of subjects during withdrawal from cannabis use will maximize our ability to detect change in pain perception and sensitivity to pain will be heightened at this time. The proposed research methods will examine the galvanic skin response, a measure of skin conductance and autonomic reactivity, during an unpleasant but safe cutaneous stimulation that has been used in other studies. We hypothesize that cannabis smokers will exhibit increased sensitivity to pain during the peak withdrawal period compared to controls. This increased sensitivity to pain in cannabis smokers will likely be observed as an increased galvanic skin response in anticipation of, and during fearful stimuli. Furthermore, in anticipation and response to this stimulus, it is expected that patients in early cannabis withdrawal will exhibit increased BOLD activation of the amygdala, ventral striatum and prefrontal cortex. The exploration of specific autonomic and brain changes in cannabis smokers will establish a basis for future genetic studies of cannabis dependence and brain-based endophenotypes. Understanding the differences between the brain and autonomic nervous systems of cannabis smokers and non-smokers will form a basis for future studies of cannabis dependence and ultimately help us develop more effective treatments for the disorder. [unreadable] [unreadable] [unreadable]